Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAE3MX4)

• DOT Name: Microtubule-associated protein RP/EB family member 2 (MAPRE2)
• Synonyms: APC-binding protein EB2; End-binding protein 2; EB2
• Gene Name: MAPRE2
• Related Disease:
  Multiple benign circumferential skin creases on limbs 1
  Nephropathy
  Familial adenomatous polyposis
  Hepatocellular carcinoma
  Leukemia
  Neoplasm
  Squamous cell carcinoma
  Ulcerative colitis
  Skin creases, congenital symmetric circumferential, 2
  Multiple benign circumferential skin creases on limbs
• UniProt ID: MARE2_HUMAN
• Pfam ID: PF00307 ; PF03271
• Sequence:
  MPGPTQTLSPNGENNNDIIQDNNGTIIPFRKHTVRGERSYSWGMAVNVYSTSITQETMSR
  HDIIAWVNDIVSLNYTKVEQLCSGAAYCQFMDMLFPGCISLKKVKFQAKLEHEYIHNFKL
  LQASFKRMNVDKVIPVEKLVKGRFQDNLDFIQWFKKFYDANYDGKEYDPVEARQGQDAIP
  PPDPGEQIFNLPKKSHHANSPTAGAAKSSPAAKPGSTPSRPSSAKRASSSGSASKSDKDL
  ETQVIQLNEQVHSLKLALEGVEKERDFYFGKLREIELLCQEHGQENDDLVQRLMDILYAS
  EEHEGHTEEPEAEEQAHEQQPPQQEEY
• Function: May be involved in microtubule polymerization, and spindle function by stabilizing microtubules and anchoring them at centrosomes. May play a role in cell migration.
• Tissue Specificity: Expressed in different tumor cell lines. Up-regulated in activated B- and T-lymphocytes.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple benign circumferential skin creases on limbs 1	DIS6BAPZ	Definitive	Autosomal recessive	[1]
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[2]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Leukemia	DISNAKFL	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[7]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[8]
Skin creases, congenital symmetric circumferential, 2	DISJTYAL	Moderate	Autosomal dominant	[9]
Multiple benign circumferential skin creases on limbs	DISZB59K	Supportive	Autosomal dominant	[1]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[12]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[13]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[13]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[14]
Rofecoxib	DM3P5DA	Approved	Rofecoxib decreases the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[15]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[18]
Okadaic acid	DM47CO1	Investigative	Okadaic acid affects the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[19]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[20]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Microtubule-associated protein RP/EB family member 2 (MAPRE2).	[17]

References

• [1] Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type. Am J Hum Genet. 2015 Dec 3;97(6):790-800. doi: 10.1016/j.ajhg.2015.10.014.
• [2] The genetic background difference between diabetic patients with and without nephropathy in a Taiwanese population by linkage disequilibrium mapping using 382 autosomal STR markers.Genet Test Mol Biomarkers. 2010 Jun;14(3):433-8. doi: 10.1089/gtmb.2009.0179.
• [3] Absence of somatic alterations of the EB1 gene adenomatous polyposis coli-associated protein in human sporadic colorectal cancers.Br J Cancer. 1998 Nov;78(10):1356-60. doi: 10.1038/bjc.1998.684.
• [4] Proteomic profiling reveals the prognostic value of adenomatous polyposis coli-end-binding protein 1 in hepatocellular carcinoma.Hepatology. 2008 Dec;48(6):1851-63. doi: 10.1002/hep.22552.
• [5] The effects of siRNA-mediated inhibition of E2A-PBX1 on EB-1 and Wnt16b expression in the 697 pre-B leukemia cell line.Haematologica. 2006 Jun;91(6):765-71.
• [6] Clinical relevance of cytoskeleton associated proteins for ovarian cancer.J Cancer Res Clin Oncol. 2018 Nov;144(11):2195-2205. doi: 10.1007/s00432-018-2710-9. Epub 2018 Aug 9.
• [7] End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.Clin Chim Acta. 2016 Aug 1;459:45-52. doi: 10.1016/j.cca.2016.05.012. Epub 2016 May 18.
• [8] EB1 protein alteration characterizes sporadic but not ulcerative colitis associated colorectal cancer.Oncotarget. 2017 Jul 4;8(33):54939-54950. doi: 10.18632/oncotarget.18978. eCollection 2017 Aug 15.
• [9] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [12] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [14] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [17] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [18] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [19] The marine toxin okadaic acid induces alterations in the expression level of cancer-related genes in human neuronal cells. Ecotoxicol Environ Saf. 2013 Jun;92:303-11. doi: 10.1016/j.ecoenv.2013.03.009. Epub 2013 Apr 3.
• [20] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.